Rapid Eye Movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by acting out of dreams. Older individuals with RBD frequently develop Parkinson Disease (PD), Dementia with Lewy Bodies (DLB), or Multiple System atrophy (MSA)?collectively termed synucleinopathies?within several years, indicating that RBD is a signal that one of these neurodegenerative diseases has taken root. RBD represents a preclinical stage of synucleionopathy, when brain changes are present but neurodegenerative symptoms have not yet appeared. Subsequently, RBD offers an opportunity to test potential treatments for synucleinopathy at the earliest stages of disease when treatment is most likely to be effective. Based on current information about treatments in the pipeline for synucleinopathies, we anticipate a clinical trial in RBD to protect against synucleinopathy in 2-3 years. However, several gaps prohibit proceeding with a clinical trial currently, including 1) lack of coordination between sites that follow relatively small cohorts, 2) no biomarkers for synucleinopathy, 3) lack of standardization of clinical assessment across sites, 4) 5) lack of a coordinated effort to direct and specifically plan for a neuroprotective clinical trial. To address these gaps, we propose to form the North American Preclinical Synucleinopathy (NAPS) Consortium. The aims are to form a joint registry of RBD patients, establish standardized assessments and biomarker collection across sites, and institute an expert panel to guide decisions for the NAPS Consortium toward a clinical trial. Through these aims, the NAPS Consortium will build the framework necessary for a successful clinical trial in RBD, including a large and ready patient cohort, standardized functional and biofluid markers, ability to easily scale to new sites, and a clear organizational structure to co-ordinate a multi-site study. The ultimately goal is a successful trial in RBD that can be extended to the general population, to identify and stop PD, DLB, and MSA before any symptoms appear.